Bendamustine-Bortezomib-Desametasone (BVD) in the Management of Relapsed and Refractory Multiple Myeloma : A REAL-Life Experience

Introduction:

Bendamustine is a bifunctional alkylating agent, with low toxicity, proved to be effective in relapsed, refractory and in new diagnosed Multiple Myeloma (MM).

It has been evaluated efficacy and tolerance of Bendamustine, in combination with bortezomib-dexametasone (BVD) in patients with relapsed and refractory MM (rrMM), whose prognosis is particularly severe. A regional retrospective real-life analysis of patients with rrMM who had been treated with BVD as salvage therapy has been performed.

Methods:

35 patients (19 M/16 F), with rrMM, median age at diagnosis 57 years (r. 36-82), median age at start of treatment 62 years (r.37-83) treated with several lines of treatments (median 6, r. 2-11), every refractory to all the drugs previously received (also Bortezomib), received BVD (Bendamustine 90mg/sqm days 1,2; Bortezomib 1.3mg/sqm days 1,4,8,11, Desametasone 20mg days 1,2,4,5,8,9,11,12, Pegfilgrastim day +4) every 28 days, until progression.

ISS was equally distributed, and cytogenetic was evaluable in 9 patients, and in particular one del13q and one t(11;14). All the patients had previously been treated with schedule containing bortezomib and IMIDs, 90% of them with melphalan, 77% with cyclophosphamide, 34% with antracyclines and 30% had also received radiotherapy. 58% of them had undergone at least to a single auSCT. All patients were relapsed and refractory to last therapies received before BVD.

Results:

Bendamustine was well tolerated, with grade 3 transfusion-dependent anemia in 29% of patients, and 41% grade 3 neutropenia (no ospedalization was required, no septic shocks were observed). No severe extrahematologic toxicity was observed, only grade 1 gastrointestinal side effect (nausea), treated by common antiemetic drugs.

According to IMWG, after a median follow-up of 9 months (r.2-36), ORR was 54% (1 CR, 1 VGPR, 9 PR, 8 MR) with 7 PD and 9 patients in SD, which can be considered as an impressive result in this subset of rrMM patients. In particular, for 4 patients, BVD was, after having achieved a PR, a bridge to second auSCT, and for one patient a bridge to auSCT.

Median OS from diagnosis was 61.4 months (range 6-151), median OS from start of Bendamustine was 7.2 months (range 2-36).

Conclusion:

BVD has shown significant efficacy (ORR 54%) in a particular severe setting of patients, relapsed and refractory to all avaiable therapeutic resources, and in particular cases it could be considered as a bridge to a second autologous or allogenic BMT.